The invention relates to a remarkably simple method for the in vitro production of three-dimensional, vital and mechanically stable cartilage or bone tissue and to the use thereof as a transplantation material for treating cartilage or bone defects and degenerative diseases such as rheumatism or arthrosis, and to the use thereof in testing active substances and physical factors. The invention is also directed to the cartilage or bone tissue and therapeutical formulations produced thereby, e.g. injection solutions comprising such tissue. According to the invention, most various cartilage and bone tissues can be produced, e.g. hyaline, elastic, fibrous, or connective tissue cartilages such as joint cartilage, nose cartilage, meniscus cartilage, or intervertebral cartilage.
In the field of tissue engineering, solutions to build up endogenous tissue have been sought for quite some time. To this end, endogenous cells with and without support material have been used on the one hand, and, on the other hand, support materials exclusively have been incorporated in the defect where, depending on the indication, it is possible to use absorbable or non-absorbable materials.
The use of support materials is disadvantageous in that decomposition products thereof may affect other tissues, and when using non-autogenous support materials, i.e., those not derived from the patient, immune reactions or infections with animal or human pathogens may arise.
One familiar method using endogenous cells is transplantation of cartilage and bone cells, which is used in the treatment of cartilage and bone defects. In this method, the potential of cartilage and bone cells is utilized to build up new tissue in vivo. Thus, for example, cartilage or bone biopsies are taken from a patient, cartilage or bone cells are isolated therefrom, grown by means of cell culturing, and the cells are subsequently transplanted into the patient in the region of the tissue defect, e.g. by injecting. There, the cells form new tissue, thus effecting complete repletion of the defect.
The above-mentioned methods achieve build up of tissue in the body subsequent to applying the cell transplant or incorporating the support materials.
However, tissue engineering is also directed to the in vitro prefabrication of endogenous tissue. A variety of methods are known from the literature (cf., DE 195 40 487, WO 97/46665, DE 197 52 900, U.S. Pat. No. 5,932,459), which methods require special apparatus or supports, involve numerous process steps, or necessitate addition of growth-stimulating compounds representing foreign substances to the body. It was therefore the object of the present invention to provide a preferably simple method of producing typical cartilage or bone tissue, which method allows for the production of vital, three-dimensional and mechanically stable tissue which is suitable for transplantation and ensures rapid adhesion in the body and rapid repletion of the cartilage or bone defect. Furthermore, the tissue produced in vitro should not trigger any immunological reaction in the organism receiving the transplant.